JBC Reflections looks at breakthroughs in Gaucher disease

Roscoe Brady in 1986 administering macrophage-targeted glucocerebrosidase to a young patient with Gaucher disease.

While medical breakthroughs generate tremendous news, little thought is given to the countless basic discoveries that provide the foundations for that clinical endpoint. In a new Journal of Biological Chemistry “Reflections” article, Roscoe O. Brady, a scientist emeritus at the National Institutes of Health, offers some perspective about this long and sometimes arduous journey.

In Brady’s case, he details his work in studying the synthesis and metabolism of long-chain fatty acids. Over the course of many years, a few simple questions, experiments and observations would eventually lead to the discovery of the enzyme glucocerebrosidase (which cleaves glucose head groups off cerebroside lipids) and its deficiency as the underlying cause of Gaucher disease.

This key scientific moment would lead not only to uncovering the defects in other inherited metabolic storage disorders, such as Fabry or Tay-Sachs disease, but also to the development of enzyme replacement therapy, which was approved for Gaucher disease in 1991 and has since helped treat thousands of Gaucher patients.